Malignant melanoma (MM) is a malignant tumor of pigment-producing cells (melanocytes) which primarily occur in the skin, but is also noted in the eyes, ears, oral cavity, digestive tract, genital mucosa, and leptomeninges (1). The yearly incidences in Japan and the European Union are 0.93 and 12.41 per 100,000 people respectively (4). Secondary metastatic pleural melanoma is rare and usually occurs in pulmonary metastasis. Only 2% of melanoma patients with intrathoracic metastasis develop malignant pleural effusion (3).
There are few reports of recurrent malignant melanoma mainly presenting with pleural effusions in the literature (5–18) (Table 1); all were confirmed by pathology.
Metastasic pleural effusion is more frequent in males, with a ratio of approximately 11:4 with most of the patients being > 40 years old (Table 2). According to a previous study, the age of patients with metastatic melanoma to the thorax varies from 16 to 79 years (mean, 51 .9) and the male-to-female incidence ratio is approximately 1.6:1 (3). Most malignant melanomas originated from skin areas such as trunk and limbs but can also be mucosal such as the oral, cilioretinal, and choroidal.
The duration from diagnosis of the primary cancer to thoracic metastasis averages 32 months. However, the range is wide and pulmonary metastasis occurred 12 and 15 years after the initial diagnosis for two patients (19). There is no study done on the period of malignant melanoma metastasis to the pleura. In our review, the time-lapse from the primary tumor to the detection of pleural metastasis is from 8 months to 16 years (mean, 4.9 years). Two patients were diagnosed with pleural metastatic melanoma using pleural biopsy histopathologic findings having denied having a medical history of malignant melanoma. Choroidal and oral malignant melanoma were also later discovered (11, 12). It may be postulated that concealment of the primary lesion caused delayed diagnosis. The longest recorded time from the primary tumor to pleural metastasis is 16(13) years. The patient presented with left-sided massive pleural effusion; thoracoscopic pleural biopsy revealed metastatic malignant melanoma. The patient had malignant melanoma of the scalp 16 years prior (13) and later acknowledged a history of right heel surgery for cutaneous melanoma.
The clinical presentation of the disease is nonspecific, including; shortness of breath, chest pain, cough, and weight loss (Table 2). Therefore search for primary lesions is essential. It is known that primary cutaneous amelanotic melanoma may disappear during an advanced course (20). Abdominal pain is a rare sign of malignant melanoma that was discussed by Mytinger AK.et al. (15) (Table 3). Anand, K.et al. (13) reported an unusual patient with chronic lymphocytic leukemia (CLL) with recurrent pleural effusions, indicating that T-cell dysregulation and dysfunction in CLL may increase the risk of recurrence or secondary malignancies. A 63-year-old man who presented with black-colored pus (pyopneumothorax) resulting from an infected pleural effusion (positive for Pseudomonas) and related to metastatic malignant melanoma of the skin was discussed by Patel, G.et al (14).
Unilateral pleural effusion with or without pleural nodules, pleural thickening, pulmonary nodules, mediastinal lymphadenopathy, or calcification is the most common finding on imaging (Table 2, 3). W. Richard et al. reported (19) that 10 of 65 malignant melanoma patients that had thoracic metastasis presented with pleural effusion and 80% of them were unilateral pleural effusion. For our patient, the left pleura was significantly thickened and calcified so that the puncture needle had significant resistance to entry. Pleural thickening can indicate several diseases, such as malignant mesothelioma, tuberculous pleuritis, primary or secondary pleural lymphoma, metastatic lung cancer, ectopic thymoma, and sarcomatoid carcinoma (21). The differential diagnosis included mesothelioma, adenocarcinoma, primary pleural sarcoma, thymic epithelial tumors, lymphoma, and other metastatic tumors (7). Tuberculosis (TB) remains a significant public health concern in China, with one million new cases every year (22). The patient was first suspected to have tuberculous pleuritis from the clinical manifestations of elevated T-SPOT with positive laboratory findings of Tuberculin purified protein derivative (PPD) skin test. However, the low ADA level indicated that the diagnosis was unlikely and she was finally diagnosed with metastatic pleural melanoma using thoracoscopy.
Pleural effusion is expected to be helpful for the diagnosis of metastatic pleural melanoma with the color being bloody, yellow, or black (Table 2). Bloody pleural effusion (BPEs) is the most common with approximately half being secondary to tumors. However, only 11% of the malignant effusions were BPEs. Other common causes of BPEs include parapneumonic and posttraumatic (23). Melanin pigment is an indicator of malignant melanoma which can distinguish this disease from other morphologically similar tumors, such as lung adenocarcinoma and malignant mesothelioma (21). However, malignant melanoma does not always present with melanin in pleural fluids which increases the difficulty of diagnosis. A combination of immunohistochemistry and immunocytochemical staining techniques are powerful tools for definitive diagnosis in cases of amelanotic or hypomelanotic melanoma (21).
The diagnostic approach involves a variety of methods such as thoracentesis, skin biopsy, lymph node biopsy, thoracoscopic pleural biopsy, and surgical operations. Thoracentesis is the most effective initial diagnostic procedure. Diagnosis was made for six patients using pleural fluid cytology, 8 by thoracoscopic pleural biopsy, and 1 through a resected specimen. It is reported that the diagnostic sensitivity of cytologic analysis ranged from 40–90% (mean; 65%) with a specificity of > 99%, since the highest reported false positive rate is 0.78% (24). Multiple examination of pleural effusion provides a better diagnosis. Medical thoracoscopy is routinely used for the assessment of undiagnosed exudative pleural effusions. Combining these methods will facilitate diagnosis in > 90% of patients that present with pleural effusion (24).
The prognosis of melanomas is dismal. Survival after radiographic detection of thoracic metastasis averaged 7 months and was not longer for patients with slow metastasizing primary malignancy (19). The typical survival time of secondary metastatic melanoma ranges between 4 and 5 months, after the diagnosis (25). Mishe'el, S. et al. (12) described a patient who presented with diffuse melanosis cutis (DMC), black pleural effusion, black urine, and died 2 weeks after admission; DMC is an extremely rare manifestation of metastatic melanoma with a poor prognosis (mean survival of ~ 4 months) (26) and was reported in approximately 0.22–0.27% of the cases (27). However, Wang, T. S. et al. reported a case of complete spontaneous regression of the metastatic lesions. Of the 15 reported metastatic pleural melanoma cases, 5 died within 6 months of diagnosis, indicating the aggressive course of the tumor. Talc and bleomycin are usually used as sclerosing agents in malignant effusion (28). Palliative treatment using pleurodesis was done in 4 of the 15 cases in our review.
In conclusion, we report a left-sided pleural effusion as a rare presentation of metastatic malignant melanoma. We also reviewed 15 reported cases of metastatic melanoma who initially presented with pleural effusion, and discussed the clinical features of metastatic pleural melanoma. A limited number of studies have been reported, although metastatic pleural melanoma is rare, and has nonspecific clinical manifestations. Pleural effusion cytology combined with thoracoscopy is an effective diagnostic method for metastatic pleural melanoma. The presence of melanocytes has improved diagnosis.